Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Erika Linde,David Bulfield,Gabriella Kervefors,Nibadita Purkait,Berit Olofsson

doi:10.1016/j.chempr.2022.01.009

Abstract

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Highlights

N- and O-arylated structural motifs are key building blocks in agrochemicals, materials, and pharmaceuticals.[1,2,3] The arylation of heteroatom nucleophiles with an electrophilic arylation reagent is a central strategy to reach diarylated compound classes, such as diaryl ethers and diarylamines
Monoarylation of heteroatom nucleophiles can be achieved through the industrially important nucleophilic aromatic substitution (SNAr) methodology, the scope is limited by the requirement for either highly reactive reagents with strong electron-withdrawing groups (EWG) or harsh reaction conditions with strong bases or elevated temperatures (Scheme 1A).[4]
We present the realization of this strategy, which enables a metal-free, high-yielding difunctionalization of N- and O-nucleophiles with two different aryl groups in a single reaction (Scheme 1D)

Summary

Introduction

N- and O-arylated structural motifs are key building blocks in agrochemicals, materials, and pharmaceuticals.[1,2,3] The arylation of heteroatom nucleophiles with an electrophilic arylation reagent is a central strategy to reach diarylated compound classes, such as diaryl ethers and diarylamines. We speculated that the unusual structure of this reagent might enable an initial SNAr reaction instead of the usual ligand coupling (LC) pathway[11,35] to deliver a unique iodine(III) intermediate that could undergo a subsequent aryl transfer to yield a diarylated product.

Results

Conclusion